The hormone auxin regulates virtually every aspect of plant growth and development. Genetic and molecular studies with Arabidopsis have defined the SCFTIR1 ubiquitin-ligase complex as a positive regulator of auxin response. Recent findings indicate that auxin promotes SCFTIR1-mediated ubiquitination of the Aux/IAA proteins, a large family of transcriptional regulators which negatively regulate auxin response. The subsequent proteasome-mediated degradation of the Aux/IAAs derepresses the auxin response pathway resulting in changes in growth and development. We have shown that Aux/IAA proteins physically interact with the SCFTIR1 complex in crude seedling extracts. Auxin promotes Aux/IAA degradation by targeting these factors to the SCFTIR1 ubiquitin-ligase by an undetermined mechanism. Elucidation of how auxin regulates this interaction will provide important information into the signaling events of the auxin response pathway upstream of the SCFTIR1 ubiquitin-ligase. The long-term goal of the proposed research is to understand the molecular mechanisms underlying auxin regulation of plant growth and development. The identification of the mechanisms underlying auxin action will provide new tools for modulating auxin response for agricultural and horticultural benefit. Further, since SCF-mediated ubiquitination is highly conserved, these studies will contribute toward our understanding of this mode of cellular regulation in all eukaryotes. The specific objectives of this proposal include; 1) elucidation of the nature and regulation of protein-protein interactions between the Aux/IAA transcriptional regulators and the SCFTIR1 ubiquitin-ligase complex; 2) the genetic and molecular analysis of a new class of Arabidopsis mutants defective in auxin response; 3) the molecular characterization of a mutant derivative of the AtCUL1 SCF subunit; and 4) investigate the biological significance of the interaction between the AXR2 Aux/IAA protein and the COP9 signalosome subunit CSN5.